Long-term maintenance capecitabine and celecoxib improved clinical outcomes by targeting colorectal cancer micrometastasis

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 14513-14513
Author(s):  
M. Zhang ◽  
S. Curley ◽  
C. Ng ◽  
B. Kurland ◽  
S. Krishnan ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Stage Iv ◽  
Complete Response ◽  
Kaplan Meier ◽  
Stage Iv Disease ◽  
Disease Site ◽  
Colorectal Cancer Patients

14513 Background: Role of mainteance therapy after achieving complete response (CR) remain undefined for patients with metasatic colorectal cancer. We studied prognostic and treatment factors including maintenance capecitabine and celecoxib (XCEL) in all 19 unresectable metastatic colorectal cancer patients (pts) who had CR from the prior XCEL study. Methods: Event charts are used to summarize the timeline of the various treatments. Kaplan-Meier survival estimates and univariate log-rank tests were used to evaluate RFS and OS as time from CR. Prognostic and treatment factors included: tumor size, metastasis number (9 solitary disease), site (13 being extrahepatic), stage on diagnosis (stage II versus III/IV), disease free interval prior to stage IV disease, surgery (5 R0, 3 R1–2 resections), lactate dehydrogenase levels, first-line irinotecan chemotherapy, radiation (9 pts ≥ 45 Gy, 3 Pts < 45 Gy), and maintenance XCEL (duration 0–50.3 months). Results: Nine of 19 patients experienced recurrence (median 13 months after CR), and 4 died during the follow-up period (median 31 months after CR). The 2-year RFS for the unresected and R1–2 resected patients was 71% versus 20% for the R0 resected patients (p = 0.07). This paradoxical RFS pattern corresponded to a RFS advantage for maintenance XCEL (p = 0.002), but not any other prognostic or treatment factors. All relapses occurred in situ following discontinuation of XCEL except for the surgical cases. Patients undergoing maintenance XCEL also benefited in OS (p = 0.04). The median OS from XCEL and from onset of metastasis reached 51.9 months (95% CI, 45 months- not reached [NR]) and 73.3 months (95% CI, NR-NR months) respectively. Conclusions: Maintenance XCEL targets colorectal micrometastases and produces a paradoxical RFS and OS advantage among the high-risk unresected/R1–2 resected patients than R0 resected patients. Prospective studies are warranted to validate roles of maintenance XCEL in the treatment of colorectal micrometastases. No significant financial relationships to disclose.

Role of surgical resection among chemotherapy-treated patients with colorectal cancer stage IV disease: A survival analysis.

2011 ◽  
Vol 29 (15_suppl) ◽  
pp. 3564-3564 ◽  
Author(s):  
B. S. Lin ◽  
A. Ziogas ◽  
T. E. Seery ◽  
M. J. Stamos ◽  
J. A. Zell
Keyword(s):  
Colorectal Cancer ◽  
Survival Analysis ◽  
Surgical Resection ◽  
Stage Iv ◽  
Cancer Stage ◽  
Stage Iv Disease

Incidence of peripheral neuropathy in patients with colorectal cancer receiving oxaliplatin alone vs. radiation therapy and oxaliplatin.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e18281-e18281
Author(s):  
Matthew Blake Lockwood ◽  
Krishna Prasad Joshi ◽  
James Mobley ◽  
Suneetha Sampath ◽  
Eric R Siegel ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Rectal Cancer ◽  
Radiation Therapy ◽  
Peripheral Neuropathy ◽  
Stage Iv ◽  
Sensory Neuropathy ◽  
Chi Square ◽  
Stage Iv Disease ◽  
Nerve Fibrosis ◽  
Colorectal Cancer Patients

e18281 Background: Peripheral sensory neuropathy (PN) is a known dose limiting toxicity of oxaliplatin, used to treat patients with colorectal cancer. Patients with rectal cancer receive radiation therapy (RT) in addition to oxaliplatin in adjuvant setting. Pelvic radiation causes plexopathy due to demyelination, ischemia due to blood-vessel injury, and nerve fibrosis. To assess if RT increases the incidence of peripheral neuropathy, we conducted an analysis of patients with colorectal cancer treated with oxaliplatin alone vs. oxaliplatin and radiation. Methods: A retrospective analysis of subjects with stages II, III, and IV rectal (R) and colon (C) cancer from 2005 to 2014 was conducted. Only subjects receiving O with or without RT were included. The incidence of PN was compared for increase in subjects receiving both O and RT compared to O alone via one-sided chi-square tests at 5% alpha, both overall and after subgrouping by stage. Results: Out of 261 subjects analyzed, 158 met the study’s criteria. There were 97 C (all received only O) and 61 R (10 received only O; 51 received O+RT). PN occurred in 37% (19/51) of subjects receiving O+RT compared to 22% (24/107) receiving only O ( P= 0.025). In Stage II-III disease, PN occurred at nearly equal rates of 36% (14/39) in subjects receiving O+RT and 33% (16/46) in subjects receiving O only ( P= 0.457). However, in Stage IV disease, PN occurred in 42% (5/12) of subjects receiving O+RT compared to 13% (8/61) of subjects receiving only O ( P= 0.009). Conclusions: In our study, the incidence of PN was higher in subjects receiving both RT and O compared to O alone. Although our study did not show higher PN in stages II and III disease, patients with rectal cancer may have residual neurotoxicity from previous radiation and the subsequent exposure to oxaliplatin may be contributing to the cumulative toxicity. [Table: see text]

Immunomagnetic Enrichment and Detection of Micrometastases in Colorectal Cancer: Correlation With Established Clinical Parameters

2002 ◽  
Vol 20 (21) ◽  
pp. 4338-4343 ◽  
Author(s):  
Martin R. Weihrauch ◽  
Edmund Skibowski ◽  
Thomas C. Koslowsky ◽  
Wilfried Voiss ◽  
Daniel Re ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Bone Marrow ◽  
Cancer Patients ◽  
Stage Iv ◽  
Stage I ◽  
Clinical Parameters ◽  
Uicc Stage ◽  
Detection Rates ◽  
Stage Iv Disease ◽  
Colorectal Cancer Patients

PURPOSE: Micrometastatic disease in bone marrow is of prognostic significance in colorectal cancer patients. However, detection rates of standard immunocytology are relatively low. We used magnetic activated cell sorting (MACS), a highly sensitive method, to increase detection rates and correlated the presence of cytokeratin (CK)-expressing cells with clinical parameters. PATIENTS AND METHODS: Bone marrow was obtained from 51 consecutive patients with newly diagnosed colorectal adenocarcinoma who underwent primary surgery and 18 control subjects. International Union Against Cancer (UICC) stage I disease was diagnosed in 11 patients, stage II disease was diagnosed in 14 patients, stage III disease was diagnosed in 12 patients, and stage IV disease was diagnosed in 14 patients. CK-positive cells were enriched and stained with magnetically labeled CAM 5.2 antibodies directed to CK 7 and 8. RESULTS: CK-positive cells were found in 33 (65%) patients and were absent in 18 (35%). Four of 11 (36%) patients with UICC stage I disease, nine of 14 (64%) with stage II diease, eight of 12 (67%) with stage III disease, and 12 of 14 (86%) with stage IV disease were CK-positive. Epithelial cells were more frequently found in pT3/4 (72%) than in pT1/2 (36%) tumors (P = .026), but there was no difference for lymph node status. CK-positive patients had a higher chance for elevated carcinoembryonic antigen (85% v 15%, P = NS) and CA 19-9 levels (92% v 8%, P = .019). There were no significant differences in CA 72-4, sex, age, tumor grading, or tumor localization regarding the presence of CK-positive cells. All control subjects were CK-negative. CONCLUSION: In searching for micrometastases in colorectal cancer patients, we have achieved high detection rates by using MACS. The presence of these cells correlated significantly with tumor stage, tumor extension, and the tumor marker CA 19-9.

Contemporary multi-modal management of colorectal cancer: Evolving patterns of care in an Irish cohort.

2018 ◽  
Vol 36 (4_suppl) ◽  
pp. 827-827
Author(s):  
Megan Greally ◽  
Emily Harrold ◽  
Helen M Fenlon ◽  
Donna Eaton ◽  
Jim McCarthy ◽  
...  
Keyword(s):  
De Novo ◽  
Stage Iv ◽  
Best Supportive Care ◽  
Kaplan Meier ◽  
Pet Ct ◽  
Symptomatic Relapse ◽  
Stage Iv Disease ◽  
The Impact ◽  
Term Benefit

827 Background: The last 15 years have seen significant improvements in the outcomes of patients (pts) with CRC. More effective systemic therapy (Rx) and wider use of surgery (Sx) in stage IV disease (Dx) are key drivers of this. We evaluated the impact of intense surveillance in concert with greater use of metastasectomy and improved systemic Rx on CRC outcomes. Methods: This is a retrospective review of the clinical, radiologic and histological records for consecutive pts with CRC who were referred to the multi-disciplinary CRC team from 2003-2016. Pts with stage I/II Dx were included when referred for adjuvant Rx for high-risk features. We recorded pt characteristics, Rx received and outcomes. Survival was assessed using Kaplan-Meier analysis. Results: We identified 600 pts. Median age was 65 (22-97 years). 71.2% (n=427) of pts had left sided CRC and 25.7% (n=154) had right sided Dx. 211 pts (35.2%) had de novo metastatic Dx. 163 of 389 pts (41.9%) with stage II/III disease relapsed. Median Dx-free interval was 16 months. Of 163 relapses, 121 (74%) were detected by radiologic surveillance and 14 (9%) by rise in CEA. Symptomatic relapse occurred in 20 pts (12%). Median overall survival (OS) was significantly improved in pts with relapse detected by CT, PET/CT or CEA rise (54, 53 and 54 months respectively) vs pts with symptomatic relapse (4 months, p<0.001). Metastasectomy rates were higher in pts with image-detected relapse ( p=0.017). Median OS for pts with stage IV CRC who received any Rx was 27 months. Pts with right sided Dx had shorter median OS vs pts with left sided Dx (24 months vs 40 months, p=0.002). 195 pts (52.8%) underwent metastasectomy; median OS was 71 months vs 16 months in those who did not undergo Sx. 84 pts (14%) with stage IV CRC are currently Dx-free after Sx. Median OS was improved with increasing lines of Rx. Survival in pts receiving best supportive care was 5 months vs 17, 25, 34, 38 and 42 months for pts receiving 2, 3, 4 and 5 lines of Rx respectively ( p<0.001). Conclusions: CRC outcomes are improving with effective multi-disciplinary care, close surveillance, sequencing of systemic Rx and judicious use of salvage Sx following relapse. Our findings support long-term benefit for surgical metatastectomy in stage IV CRC.

scholarly journals Immune status is prognostic for poor survival in colorectal cancer patients and is associated with tumour hypoxia

2020 ◽  
Vol 123 (8) ◽  
pp. 1280-1288 ◽  
Author(s):  
Stephanie G. Craig ◽  
Matthew P. Humphries ◽  
Matthew Alderdice ◽  
Victoria Bingham ◽  
Susan D. Richman ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Stage Iv ◽  
Tumour Hypoxia ◽  
Poor Survival ◽  
Cell Counts ◽  
Tumour Bulk ◽  
Stage Iv Disease ◽  
Colorectal Cancer Patients ◽  
Hypoxia Signature

Abstract Background Immunohistochemical quantification of the immune response is prognostic for colorectal cancer (CRC). Here, we evaluate the suitability of alternative immune classifiers on prognosis and assess whether they relate to biological features amenable to targeted therapy. Methods Overall survival by immune (CD3, CD4, CD8, CD20 and FOXP3) and immune-checkpoint (ICOS, IDO-1 and PD-L1) biomarkers in independent CRC cohorts was evaluated. Matched mutational and transcriptomic data were interrogated to identify associated biology. Results Determination of immune-cold tumours by combined low-density cell counts of CD3, CD4 and CD8 immunohistochemistry constituted the best prognosticator across stage II–IV CRC, particularly in patients with stage IV disease (HR 1.98 [95% CI: 1.47–2.67]). These immune-cold CRCs were associated with tumour hypoxia, confirmed using CAIX immunohistochemistry (P = 0.0009), which may mediate disease progression through common biology (KRAS mutations, CRIS-B subtype and SPP1 mRNA overexpression). Conclusions Given the significantly poorer survival of immune-cold CRC patients, these data illustrate that assessment of CD4-expressing cells complements low CD3 and CD8 immunohistochemical quantification in the tumour bulk, potentially facilitating immunophenotyping of patient biopsies to predict prognosis. In addition, we found immune-cold CRCs to associate with a difficult-to-treat, poor prognosis hypoxia signature, indicating that these patients may benefit from hypoxia-targeting clinical trials.

Circulating Tumor Cells Count Predicts Survival in Colorectal Cancer Patients

2014 ◽  
Vol 23 (3) ◽  
pp. 279-284 ◽  
Author(s):  
Adriana Romiti ◽  
Salvatore Raffa ◽  
Roberta Di Rocco ◽  
Michela Roberto ◽  
Annalisa Milano ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Overall Survival ◽  
Cancer Patients ◽  
Tumor Cells ◽  
Circulating Tumor Cells ◽  
Early Stage ◽  
Stage Iv ◽  
Quantitative Immunofluorescence ◽  
Colorectal Cancer Patients

Background & Aims: Data on the potential of circulating tumor cells (CTC) count in predicting overall survival (OS) in patients with colorectal cancer are timely and worthy of interest. This study aimed to evaluate the prognostic role of CTC count in both localized and metastatic colorectal cancer patients.Methods: Consecutive patients with histological diagnosis of colorectal cancer were enrolled. CTC count was performed, by using a quantitative immunofluorescence method, at baseline (T0) and 1 month following start of chemotherapy (T1). A CTC count <2 was considered negative, whilst a CTC level ≥2 was positive. Overall survival was calculated accordingly.Results: A total of 75 colorectal cancer patients were enrolled, including 54 stages I-III and 21 stage IV patients. Overall, 21 (28%) patients had a positive CTC count at baseline, and it was significantly associated with a worse prognosis as compared to a negative status (OS: 36.2 vs. 61.6 months; P = 0.002). CTC count remained positive after chemotherapy in 22.4% of the patients and it was an independent prognostic factor of OS (P = 0.03; Hazard Ratio: 3.55; 95% CI: 1.1-11.5).Conclusions: This study found that the presence of CTCs is associated with a reduced survival in colorectal cancer patients. Further studies aimed at testing such a predictive value in early stage colorectal cancer are awaited.

Phosphorylated Akt and MAPK expression in primary tumors and in corresponding metastases and clinical outcome in colorectal cancer patients receiving irinotecan-cetuximab.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e14086-e14086
Author(s):  
Riccardo Giampieri ◽  
Mario Scartozzi ◽  
Elena Maccaroni ◽  
Alessandra Mandolesi ◽  
Simona Biagetti ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Cancer Patients ◽  
Progression Free Survival ◽  
Primary Tumors ◽  
Kaplan Meier ◽  
Phosphorylated Akt ◽  
Line Setting ◽  
Colorectal Cancer Patients

e14086 Background: Other than the well-known EGFR pathway activation via the Ras-Raf-MAP-kinase, a possible role of other potential biomarkers could be relevant in determining resistance to anti-EGFR treatment, such as the protein-serine/threonine kinase Akt. We tried to assess the role of Akt and MAPK expression in metastatic colorectal cancer patients and their relationship with outcome for patients receiving Irinotecan-Cetuximab. Methods: Eligible patients were metastatic colorectal cancer patients treated in 2nd or 3rd line setting with a irinotecan-cetuximab based regimen. Patients were tested for K-ras status and subsequently assessed by immunoistochemistry for pAkt and MAPK expression, both in primary tumours and metastases whenever sufficient tissue was available. The role of pAkt and MAPK expression was evaluated for K-ras wild type patients for different likelihood of response, overall survival and progression free survival. Response was evaluated by RECIST criteria. Survival analysis was performed via Kaplan-Meier method. Results: In metastases pAkt correlated with RR (9% vs. 58%, p=0.004), PFS (2.3 months vs.9.2 months p < 0.0001) and OS (6.1 months vs.26.7 months p < 0.0001) and pMAPK correlated with RR (10% vs, 47%, p = 0.002), PFS (2.3 months vs.8.6 months p < 0.0001) and OS (7.8 months vs.26 months p=0.0004). At multivariate analysis pAkt and pMAPK in metastases were able to independently predict PFS. pAkt in metastases independently correlated with RR as well. Conclusions: pAkt and pMAPK expression in metastases may modulate the activity of EGFR-targeted antibodies. We could speculate that in patients with pAkt and pMAPK metastases expression targeting these factors may be crucial.

Prognostic role of aberrant mTOR activation in patients with stage II and III colorectal cancer

2020 ◽  
Vol 14 (12) ◽  
pp. 1127-1137
Author(s):  
Tong-Tong Zhang ◽  
Yi-Qing Zhu ◽  
Hong-Qing Cai ◽  
Jun-Wen Zheng ◽  
Jia-Jie Hao ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cox Regression ◽  
Disease Free Survival ◽  
Stage Ii ◽  
Poor Prognostic Factor ◽  
Cox Regression Analysis ◽  
Kaplan Meier ◽  
Potential Biomarker ◽  
Risk Predictor

Aim: This study aimed to develop an effective risk predictor for patients with stage II and III colorectal cancer (CRC). Materials & methods: The prognostic value of p-mTOR (Ser2448) levels was analyzed using Kaplan–Meier survival analysis and Cox regression analysis. Results: The levels of p-mTOR were increased in CRC specimens and significantly correlated with poor prognosis in patients with stage II and III CRC. Notably, the p-mTOR level was an independent poor prognostic factor for disease-free survival and overall survival in stage II CRC. Conclusion: Aberrant mTOR activation was significantly associated with the risk of recurrence or death in patients with stage II and III CRC, thus this activated proteins that may serve as a potential biomarker for high-risk CRC.

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